The Children’s Hospital at Saint Peter’s University Hospital Participates in a Global Phase I Gene Therapy Trial for Fatal Genetic Condition

May 19, 2021

The Children’s Hospital at Saint Peter’s University Hospital Participates in a Global Phase I Gene Therapy Trial for Fatal Genetic Condition
Nationally Recognized Lysosomal Disease Therapy Center at Saint Peter’s Doses First Patient
Suffering from Infantile GM1 Gangliosidosis in the Imagine-1 Study
New Brunswick, N.J. – May 19, 2021 – The Children’s Hospital at Saint Peter’s University Hospital has announced that it has dosed the first patient in Imagine-1, a global Phase 1/2 clinical trial program for PBGM01, an adeno-associated virus (AAV)-delivery gene therapy being developed by Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company, that is being studied for the treatment of infantile GM1 gangliosidosis (GM1), a fatal genetic condition.
Saint Peter’s was chosen as one of 10 international clinical trial sites for the global Imagine-1 study for PBGM01 by Passage Bio because of its internationally recognized geneticist with expertise in lysosomal storage diseases, Debra-Lynn Day-Salvatore, MD, PhD, FAAP, FACMG, chair of the Department of Medical Genetics and Genomic Medicine, and principal investigator for the Imagine-1 trial. Saint Peter’s is home to one of the largest comprehensive Lysosomal Disease Therapy Centers in the United States. Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. Nearly 50 of these disorders have been described to date with new lysosomal storage disorders continuing to be identified. 
GM1, a rare monogenic lysosomal storage disease, is caused by mutations in the GLB1 gene, which encodes the lysosomal enzyme beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of toxic levels of GM1 gangliosides in neurons throughout the brain, causing rapidly progressive neurodegeneration. Accumulation also results in progressive damage to other tissues including the heart, liver, and bones and manifests with hypotonia (reduced muscle tone), progressive CNS dysfunction, seizures, and rapid developmental regression. Life expectancy for infants with GM1 ranges from 2-10 years, and infantile GM1 represents approximately 60 percent of the global GM1 incidence of 0.5 to 1 in 100,000 live births.
Imagine-1 is a global study of PBGM01 administered by a single injection directly into the cisterna magna, an opening in the subarachnoid space surrounding the brain, in pediatric subjects with early and late infantile GM1. PBGM01 delivers a functional GLB1 gene encoding the β-gal enzyme to the brain and peripheral tissues that in preclinical studies showed reduced accumulation of GM1 gangliosides. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to reverse neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and high levels of expression of the β-gal enzyme in both the CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1. PBGM01 is now being tested in patients with infantile GM1 gangliosidosis to determine whether such treatment is safe and effective by showing specified improvements in neurological function, developmental potential, overall survival, and the quality of life for patients with GM1.
Dr. Day-Salvatore has attracted a multidisciplinary team of physicians and medical experts that works collaboratively to offer world-class medical care that delivers hope to parents when they have nowhere else to turn. The genetics research team at Saint Peter’s is anchored by Daniela Silva, MSN, RN, CCRN, CCRP, clinical research nurse coordinator, and, apart from other members of the Genetics Department, includes representatives from the following disciplines: Pediatric Neurology, Interventional Radiology, Neurodevelopmental Pediatrics/ Child Psychology, Pediatric Ophthalmology, Pediatric Audiology, Pediatric Anesthesiology, Pediatric Cardiology, Pharmacy, Radiology, Laboratory Medicine, Pediatric Intensive Care, Nursing staff across all disciplines, Respiratory Therapy, Child Life, Pastoral Care, and Multimedia.
Sudipta Roychowdhury, MD, sub-investigator on the Imagine-1 trial, is a diagnostic and interventional neuroradiologist, who successfully performed the delicate injection procedure. Carlos Lastra, MD, director of the Division of Pediatric Neurology and lead neurologist on the Imagine-1 study, is also a sub-investigator.
“This clinical study requires exquisite coordination,” said Dr. Day-Salvatore. “Everyone plays a pivotal role, and I am extremely proud of the teamwork, precision, and seamless work flow that resulted in the successful dosing of the first patient in the clinical trial program for PBGM01. I am also grateful to the patient’s family for entrusting us with the care of their precious child. We are pleased to celebrate this milestone with the patients, families, and researchers that helped to bring this effort to fruition and share their hope, dreams, and resolve for the future.”
About The Children’s Hospital at Saint Peter’s University Hospital
The Children’s Hospital at Saint Peter’s University Hospital is a state-designated acute care facility and Regional Perinatal Center. Saint Peter’s Children’s Hospital provides families with access to a full range of pediatric specialties, including a nationally renowned Level III Neonatal Intensive Care Unit, a dedicated Pediatric Emergency Department, adolescent medicine, cancer care, diabetes, orthopedics, surgery, developmental pediatrics, gastroenterology, allergy and immunology, infectious disease medicine, cardiology, nephrology, neurology, pediatric intensive care, pulmonary/sleep medicine, audiology and physical therapy. Other programs and services include Medical Genetics and Genomic Medicine, which counsels, tests and treats children with rare diseases; the Craniofacial and Neurosurgical Center, which offers corrective surgery and multidisciplinary support for children born with cleft lip, cleft palate and other facial deformities; the Dorothy B. Hersh Regional Child Protection Center, a state-designated regional Diagnostic and Treatment Center for child abuse prevention; and the Center for Diabetes Self-Management and Education, which diagnoses and treats children with diabetes and other endocrine disorders. Saint Peter’s Children’s Hospital is a U.S. News and World Report’s Best Children’s Hospital for Neonatology 2020-21 and has received Perinatal Certification from the Joint Commission and the Beacon Award for Excellence from the American Association of Critical-Care Nurses. The Children’s Hospital is sponsored by the Roman Catholic Diocese of Metuchen.
About The Department of Medical Genetics and Genomic Medicine at Saint Peter’s University Hospital
Saint Peter’s University Hospital has provided comprehensive clinical genetic services since 1992. As a state-designated regional center, the department provides inpatient and outpatient services to patients of all ages with a variety of genetically-influenced conditions including abnormal newborn screens, confirmed inborn errors of metabolism, birth defects, chromosome abnormalities, hearing impairment, craniofacial and genetic bone disorders, autism spectrum, cancer, and diseases of the heart, lungs, kidneys, brain, skin, muscles, eyes, gastrointestinal and genitourinary tracts. The department houses one of the largest comprehensive Lysosomal Disease Therapy Centers in the United States, trials orphan drugs, and provides a broad range of pre-conceptional, prenatal, and postnatal genetic counseling as well as pregnancy-specific management and treatment of maternal metabolic, lysosomal, and genetic conditions. Newborn screening and general genetic services at Saint Peter’s are funded in part by Special Child Health and Early Intervention Services, New Jersey Department of Health.

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